Erythema multiforme (EM) is an independent syndrome usually triggered by a viral or bacterial infection, most commonly by Herpes simplex or mycoplasma. Especially in children, a COVID-19 infection can trigger EM. A drug can also act as a trigger (in less than 10% of the cases). However, the aetiology frequently remains unknown.
According to current knowledge, drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are two forms of a separate syndrome that includes EM-like mucosal changes but the skin symptoms are different.
Patients with Stevens-Johnson syndrome or TEN must be referred immediately to specialist care.
Symptoms
Erythema multiforme
EM minor: symmetrical lesions predominantly on the limbs and face with a characteristic cockade pattern (target lesions) of 1-2 cm in diameter, which may have a small central vesicle (pictures 123456).
EM major: the rash is more severe, the vesicles are large and mucosal involvement is present (pictures 7891011).
Patients are usually young adults.
Lesions develop over a few days and do not change their location.
Mild disease forms heal spontaneously within 1-3 weeks.
Symptoms may recur.
EM will not progress into toxic epidermal necrolysis.
The patient usually has mild fever as a general symptom and feels generally ill.
Particularly mycoplasma and Chlamydia pneumoniae infections may cause, especially in children, a clinical picture where the primary symptom consists of breaks in the oral mucosa and there are only few or no findings on the skin.
Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN)
Different degrees of the same drug reaction
Stevens-Johnson syndrome (picture12) is a drug reaction with purpuric lesions involving less than 10% of total body surface area. Eroding vesicles are present on the skin and mucous membranes.
Toxic epidermal necrolysis (Lyell's syndrome) (picture 13) is a serious drug reaction with epidermal detachment involving over 30% of total body surface area and mucosal erosions. The patient will have systemic symptoms and need aggressive treatment.
The most common triggering agents are non-steroidal anti-inflammatory drugs, antimicrobial drugs, antiepileptics and allopurinol.
Diagnosis
Diagnosis is based on the clinical picture.
Histopathological findings are non-specific.
Treatment
EM minor
Mild forms of EM resolve without treatment.
If the bacterial infection that triggered the reaction is known, it should be treated.
If the reaction was triggered by a drug, the drug is discontinued.
EM major
Systemic glucocorticoids for 3-4 weeks are generally prescribed, even though no clear evidence is available on their efficacy. The starting dose of prednisone or prednisolone is 30-60 mg/day.
A dermatologist should be consulted for appropriate topical treatment.
An ophthalmologist should be consulted if the patient has eye symptoms.
Frequently recurring episodes of EM caused by the Herpes simplex virus may be an indication for prophylactic medication against herpes.
Stevens-Johnson syndrome: immediate referral to hospital
Toxic epidermal necrolysis: the patient needs high dependency/intensive care.
References
Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol 2012;51(8):889-902. [PubMed]
Mawhirt SL, Frankel D, Diaz AM. Cutaneous Manifestations in Adult Patients with COVID-19 and Dermatologic Conditions Related to the COVID-19 Pandemic in Health Care Workers. Curr Allergy Asthma Rep 2020;20(12):75. [PubMed]
Daneshgaran G, Dubin DP, Gould DJ. Cutaneous Manifestations of COVID-19: An Evidence-Based Review. Am J Clin Dermatol 2020;21(5):627-639.[PubMed]